tbuckley/cabot-search huggingface dataset:
ENVASARC: A pivotal trial of envafolimab and envafolimab in combination with ipilimumab in patients with advanced or metastatic undifferentiated pleomorphic sarcoma or myxofibrosarcoma who have progressed on prior chemotherapy.
Authors: Richard F. Riedel, Sant P. Chawla, Mihaela Druta, Robin Lewis Jones, Scott Schuetze, Joelle Lam, Dongliang Zhuang, James L. Freddo, Bonne J. Adams, Charles P. Theuer, Sandra P. D'Angelo
Journal: Journal of Clinical Oncology (2023)

TPS11583 Background: Metastatic undifferentiated pleomorphic sarcoma (UPS) and the genetically related myxofibrosarcoma (MFS) are soft tissue sarcoma (STS) subtypes with poor prognoses. While responses to first-line chemotherapy can approach 20%, efficacy remains limited in the 2 nd -line setting and beyond. Pazopanib, the only FDA approved treatment in the refractory setting, has demonstrated an objective response rate (ORR) of 4%. Envafolimab is a single domain PD-L1 antibody administered by rapid subcutaneous (SQ) injection that is approved for the treatment of microsatellite instability-high (MSI-H) cancer in China. The activity of envafolimab appears to be similar to other PD-1 antibodies administered intravenously (i.v.). Envafolimab demonstrated a 32% ORR in MSI-H colorectal cancer patients with progressive disease following three approved chemotherapeutics, similar to the ORR of 28% and 33% with nivolumab and pembrolizumab in these patients, respectively. The rationale for the ENVASARC is based on envafolimab activity in STS in phase 1 trials and previously reported activity of checkpoint inhibition in UPS/MFS: single-agent pembrolizumab demonstrated a 23% ORR, while the combination of nivolumab and ipilimumab demonstrated a 29% ORR in refractory UPS/MFS. Methods: ENVASARC (NCT 04480502) is a pivotal multicenter (at 30 U.S. and U.K. centers) open-label, randomized, non-comparative, parallel cohort study of envafolimab 600 mg every 3 weeks by SQ injection (n = 80) or envafolimab 600 mg every 3 weeks by SQ injection combined with ipilimumab 1 mg/kg every 3 weeks i.v. for four doses (n = 80) in patients with locally advanced, unresectable or metastatic UPS/MFS with disease progression on one or two lines of prior therapy. The primary objective of each of parallel cohort is to demonstrate an ORR with a lower limit of the 95% confidence interval that excludes 5.0% in each cohort. If ≥ 9 responders are observed among the 80 patients enrolled in each cohort, then the lower bound of the 95% confidence interval will exclude 5.0%. Secondary endpoints include duration of response, PFS and OS. Key inclusion criteria: ≤ 2 prior lines of therapy ([neo]adjuvant therapy excluded), ECOG ≤ 1. Clinical trial information: NCT04480502 .
Frailty trajectory predicts subsequent cognitive decline: A 26‐year population‐based longitudinal cohort study
Authors: Ruidan Li, Zheran Liu, Rendong Huang, Ye Chen, Zhigong Wei, Jingjing Wang, Ling He, Yiyan Pei, Yonglin Su, Xiaolin Hu, Xingchen Peng
Journal: MedComm (2023)

Frailty refers to a decline in the physiological functioning of one or more organ systems. It remained unclear whether variations in the trajectory of frailty over time were associated with subsequent cognitive change. The aim of the current study was to investigate the association between frailty trajectories and subsequent cognitive decline based on the Health and Retirement Study (HRS). A total of 15,454 participants were included. The frailty trajectory was assessed using the Paulson-Lichtenberg Frailty Index, while the cognitive function was evaluated using the Langa-Weir Classification. Results showed that severe frailty was significantly associated with the subsequent decline in cognitive function (
AB1033 THE RELATIONSHIP BETWEEN LONG-TERM USE OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS AND KIDNEY FUNCTION IN PATIENTS WITH ANKYLOSING SPONDYLITIS
Authors: B. S. Koo, S. Hwang, S. Y. Park, J. H. Shin, T. H. Kim
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Although nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment for ankylosing spondylitis (AS), their effect on kidney function remains unclear. <h3>Objectives</h3> This longitudinal study investigated the correlation between long-term NSAID use and kidney function in patients with AS using electronic medical records. <h3>Methods</h3> The electronic medical records of 1,280 patients with AS collected from a single center between January 2001 and December 2018 were reviewed. The Assessment of Spondyloarthritis International Society (ASAS) NSAID Intake Score was used to determine the cumulative dose of all NSAIDs prescribed for a different time intervals. Each ASAS NSAID Intake Score was obtained for intervals of 6 months, 1 year, 2 years, 3 years, 5 years, and 10 years. The correlation between the ASAS NSAID Intake Score and final estimated glomerular filtration rate (eGFR) for each interval was investigated. <h3>Results</h3> The mean ASAS Intake Scores for 6-month, 1-year, 2-year, 3-year, 5-year, and 10-year intervals were 55.30, 49.28, 44.84, 44.14, 44.61, and 41.17, respectively (Figure 1). At each interval, the pearson correlation coefficients were -0.018 (95% CI: -0.031 ‒ -0.006, p=0.004), -0.021 (95% CI: -0.039 ‒ -0.004, p=0.018), -0.045 (95% CI: -0.071 ‒ -0.019, p=0.001), -0.069 (95% CI: -0.102 ‒ -0.037, p&lt;0.001), -0.070 (95% CI: -0.114 ‒ -0.026, p=0.002), -0.019 (95% CI: -0.099 ‒ 0.062, p=0.645), respectively. There was a very weak negative relationship between ASAS Intake Score and eGFR at each interval. <h3>Conclusion</h3> Long-term NSAID use did not correlate with kidney function based on real-world data in patients with AS. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
Arginine depletion attenuates renal cystogenesis in tuberous sclerosis complex model
Authors: Athar Amleh, Hadass Pri Chen, Lana Watad, Ifat Abramovich, Bella Agranovich, Eyal Gottlieb, Iddo Z. Ben-Dov, Morris Nechama, Oded Volovelsky
Journal: Cell Reports Medicine (2023)

Cystic kidney disease is a leading cause of morbidity in patients with tuberous sclerosis complex (TSC). We characterize the misregulated metabolic pathways using cell lines, a TSC mouse model, and human kidney sections. Our study reveals a substantial perturbation in the arginine biosynthesis pathway in TSC models with overexpression of argininosuccinate synthetase 1 (ASS1). The rise in ASS1 expression is dependent on the mechanistic target of rapamycin complex 1 (mTORC1) activity. Arginine depletion prevents mTORC1 hyperactivation and cell cycle progression and averts cystogenic signaling overexpression of c-Myc and P65. Accordingly, an arginine-depleted diet substantially reduces the TSC cystic load in mice, indicating the potential therapeutic effects of arginine deprivation for the treatment of TSC-associated kidney disease.
POS1499 FACTORS ASSOCIATED WITH CARDIOVASCULAR EVENTS IN SYSTEMIC LUPUS ERYTHEMATOSUS IN A MONOCENTRIC COHORT WITH UP TO 40 YEARS OF FOLLOW-UP
Authors: N. Farina, J. Webster, W. Luo, D. Garelick, S. Moreira Pinto, D. Isenberg, A. Rahman
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is associated with an increased cardiovascular risk. Several traditional and disease-specific risk factors have been shown to correlate with the occurrence of cardiovascular events (CVE) in patients with SLE. However, results of previous studies are diverse. <h3>Objectives</h3> The objectives of this study were to report number, type and those factors associated with CVE in patients with SLE in a large, single-centre, ethnically diverse cohort with a long follow-up duration. <h3>Methods</h3> Medical records of patients treated at the Lupus Clinic at University College London Hospital (UCLH) between 1979 and 2020 were retrospectively reviewed. Data about CVE, traditional cardiovascular risk factors, demographic and disease features, and treatment history were collected. Only patients with complete available information were included in the study. Regression analyses were performed to identify factors associated with CVE. <h3>Results</h3> Four hundred and nineteen patients were included in the study. Maximum follow-up length was 40 years. Seventy-one (17%) patients had at least one CVE. Forty (50%) events were VTE, 26 (32.5%) were CVA, and 14 (17.5%) were CAD. Mean age at CVE was 44 (SD 12) years. Median time from diagnosis to CVE was 8 (IQR 4-15) years. Descriptive comparative analysis showed an increased prevalence of hypercholesterolemia (41% vs 28%, p-value=0.035), diabetes (10% vs 4%, p-value=0.027), and antiphospholipid antibodies (aPL) positivity (58% vs 27%, p-value&lt;0.001) among patients with CVE. Furthermore, these patients were treated less frequently with hydroxychloroquine (80% vs 89%, p-value=0.049). However, univariable analysis (<b>Table 1</b>) showed that only aPL positivity was significantly associated with CVE. This association was confirmed at multivariable analysis (p&lt;0.001). Survival curve for CVE according to the presence of aPL is shown in <b>Figure 1</b>. When analysing different types of CVE, aPL were specifically associated with both venous thromboembolic events (p-value&lt;0.001) and cerebrovascular events (p-value=0.007). Dedicated subanalyses revealed that cumulative glucocorticoid dose (p-value=0.010) and a diagnosis of SLE before 2000 (p-value&lt;0.001) were also significantly associated with CVE. <h3>Conclusion</h3> Cardiovascular disease is highly prevalent among patients with SLE and is associated with aPL, glucocorticoid therapy, and diagnosis before 2000. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
Policies on doctors’ declaration of interests in medical organisations: a thematic analysis
Authors: Victoria Tzortziou Brown, Margaret McCartney, Patrycja Talaga, Richard Huxtable, Andrew Papanikitas, Elizabeth David-Barrett
Journal: Journal of the Royal Society of Medicine (2023)

Objectives There has been growing concern about doctors’ conflicts of interests (COIs) but it is unclear what processes and tools exist to enable the consistent declaration and management of such interests. This study mapped existing policies across a variety of organisations and settings to better understand the degree of variation and identify opportunities for improvement. Design Thematic analysis. Setting We studied the COI policies of 31 UK and international organisations which set or influence professional standards or engage doctors in healthcare commissioning and provision settings. Participants 31 UK and international organisations. Main outcome measures Organisational policy similarities and differences. Results Most policies (29/31) referred to the need for individuals to apply judgement when deciding whether an interest is a conflict, with just over half (18/31) advocating a low threshold. Policies differed on the perception of frequency of COI, the timings of declarations, the type of interests that needed to be declared, and how COI and policy breaches should be managed. Just 14/31 policies stated a duty to report concerns in relation to COI. Only 18/31 policies advised COI would be published, while three stated that any disclosures would remain confidential. Conclusions The analysis of organisational policies revealed wide variation in what interests should be declared, when and how. This variation suggests that the current system may not be adequate to maintain a high level of professional integrity in all settings and that there is a need for better standardisation that reduces the risk of errors while addressing the needs of doctors, organisations and the public.
Associations of Internalizing and Externalizing Problems in Childhood and Adolescence With Adult Labor Market Marginalization
Authors: Iman Alaie, Pia Svedberg, Annina Ropponen, Jurgita Narusyte
Journal: JAMA Network Open (2023)

Importance Mental health problems in early life are associated with labor market marginalization, especially in youths with persistent internalizing and externalizing problems. However, previous research has not adjusted for familial (genetic and shared environmental) factors. Objective To examine associations of early-life internalizing and externalizing problems with adulthood unemployment and work disability, adjusting for familial factors. Design, Setting, and Participants This population-based prospective cohort study included Swedish twins who were born in 1985-1986 and surveyed at 4 consecutive waves across childhood and adolescence until 2005. Through linkage to nationwide registries, participants were followed up from 2006 to 2018. Data analyses were conducted between September 2022 and April 2023. Exposures Internalizing and externalizing problems, assessed with the Child Behavior Checklist. Participants were differentiated regarding duration of internalizing and externalizing problems (persistent, episodic, and noncases). Main Outcomes and Measures Unemployment (180 days or more of being unemployed) and work disability (60 days or more of being sickness absent or disability pensioned) during follow-up. Cox proportional hazards regression models were calculated to obtain cause-specific hazard ratios (HRs) with 95% CIs in the whole cohort and exposure-discordant twin pairs. Results Of 2845 participants, 1464 (51.5%) were female. Incident unemployment was experienced by 944 (33.2%) and incident work disability by 522 (18.3%) participants. Compared with noncases, persistent internalizing problems were associated with unemployment (HR, 1.56; 95% CI, 1.27-1.92) and work disability (HR, 2.32; 95% CI, 1.80-2.99). Similarly, compared with noncases, persistent externalizing problems were associated with unemployment (HR, 1.87; 95% CI, 1.55-2.26) and work disability (HR, 2.38; 95% CI, 1.87-3.03). Persistent cases had overall higher risks of adverse outcomes than episodic cases. After adjustment for familial factors, associations with unemployment were no longer statistically significant, whereas associations with work disability remained or were only slightly reduced. Conclusions and Relevance In this cohort study of young Swedish twins, familial factors explained the associations between early-life persistent internalizing and externalizing problems and unemployment; such factors were comparatively less important for the association with work disability. This suggests nonshared environmental factors may be important for the risk of future work disability among young individuals with persistent internalizing and externalizing problems.
A commentary on: “preoperative carbohydrate loading with individualized supplemental insulin in diabetic patients undergoing gastrointestinal surgery: a randomized trial”
Authors: Deqing Chen, Yingxiao Zhang, Huanhuan Huang, Zijin Qiu
Journal: International Journal of Surgery (2023)

Chen, Deqing MDa; Zhang, Yingxiao MMb; Huang, Huanhuan PhDc; Qiu, Zijin Author Information
The Emerging Paradigm of Preoperative Stereotactic Radiosurgery for Resectable Brain Metastases
Authors: Shearwood McClelland, Debra Nana Yeboa
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Variation in the management of adhesive small bowel obstruction in the Netherlands: a prospective cross-sectional study
Authors: Pepijn Krielen, Lisa P.A. Kranenburg, Martijn W.J. Stommel, Nicole D. Bouvy, Pieter J. Tanis, Jorn J. Willemsen, Jorne Migchelbrink, Rick de Ree, Esther M.G. Bormans, Harry van Goor, Richard P.G. ten Broek
Journal: International Journal of Surgery (2023)

ASBO is a frequent abdominal surgical emergency and a leading cause of morbidity and mortality in emergency surgery. The aim of this study is to provide insight into the current management of adhesive small bowel obstruction (ASBO) and associated outcomes.A nationwide prospective cross-sectional cohort study was conducted. All patients with clinical signs of ASBO admitted to participating Dutch hospitals were included during a 6 months inclusion period between April 2019 and December 2020. Ninety-day clinical outcomes were described and compared for nonoperative management (NOM) and laparoscopic and open surgery.In 34 participating hospitals, 510 patients were included, of whom 382 (74.9%) had a definitive diagnosis of ASBO. Initial management consisted of emergency surgery in 71 (18.6%) patients and NOM in 311 (81.4%) patients, 119 (31.1%) of whom required delayed surgery after failure of NOM. Surgical interventions started laparoscopically in 51.1%, of which 36.1% were converted to laparotomy. Intentional laparoscopy resulted in shorter hospital stays compared with open surgery (median 8.0 vs. 11.0 days; P <0.001) and comparable hospital mortality (5.2 vs. 4.3%; P =1.000). Oral water-soluble contrast use was associated with a decreased length of stay ( P =0.0001). Hospital stay for surgical patients was shorter in patients who were operated on within 72 h of admission ( P <0.001).This nationwide cross-sectional study demonstrates shorter hospital stay in ASBO patients who received water-soluble contrast, were operated within 72 h of admission or were operated with minimally invasive techniques. Results may support the standardization of ASBO treatment.
Cathepsin and cutaneous disorders of cornification and inflammation: their close links
Authors: Masashi Akiyama
Journal: British Journal of Dermatology (2023)

As mentioned above, the cathepsin family is a group of important proteases that are deeply involved in the development of various skin disorders of cornification and inflammation, including AiKDs. The cathepsin family members are considered to play essential roles in the keratinocyte proliferation/differentiation and inflammatory pathways in the skin.
A pro-inflammatory environment in bone marrow of Treg transplanted patients matches with graft-versus-leukemia effect
Authors: Francesco Guardalupi, Carlo Sorrentino, Giulia Corradi, Raffaella Giancola, Stefano Baldoni, Francesca Ulbar, Bianca Fabi, Rosa Andres Ejarque, Jessica Timms, Francesco Restuccia, Stella Santarone, Patrizia Accorsi, Paolo Sportoletti, Filomena De Falco, Emanuela Rosati, Alessandra Carotti, Franca Falzetti, Andrea Velardi, Massimo Fabrizio Martelli, Shahram Kordasti, Antonio Pierini, Loredana Ruggeri, Mauro Di Ianni
Journal: Leukemia (2023)
Promotion effect of TGF-β-Zfp423-ApoD pathway on lip sensory recovery after nerve sacrifice caused by nerve collateral compensation
Authors: Pingchuan Ma, Gaowei Zhang, Su Chen, Cheng Miao, Yubin Cao, Meng Wang, Wenwen Liu, Jiefei Shen, Patrick Ming-Kuen Tang, Yi Men, Li Ye, Chunjie Li
Journal: International Journal of Oral Science (2023)

Resection of oral and maxillofacial tumors is often accompanied by the inferior alveolar nerve neurectomy, resulting in abnormal sensation in lower lip. It is generally believed that spontaneous sensory recovery in this nerve injury is difficult. However, during our follow-up, patients with inferior alveolar nerve sacrifice showed different degrees of lower lip sensory recovery. In this study, a prospective cohort study was conducted to demonstrate this phenomenon and analyze the factors influencing sensory recovery. A mental nerve transection model of Thy1-YFP mice and tissue clearing technique were used to explore possible mechanisms in this process. Gene silencing and overexpression experiments were then conducted to detect the changes in cell morphology and molecular markers. In our follow-up, 75% of patients with unilateral inferior alveolar nerve neurectomy had complete sensory recovery of the lower lip 12 months postoperatively. Patients with younger age, malignant tumors, and preservation of ipsilateral buccal and lingual nerves had a shorter recovery time. The buccal nerve collateral sprouting compensation was observed in the lower lip tissue of Thy1-YFP mice. ApoD was demonstrated to be involved in axon growth and peripheral nerve sensory recovery in the animal model. TGF-β inhibited the expression of STAT3 and the transcription of ApoD in Schwann cells through Zfp423. Overall, after sacrificing the inferior alveolar nerve, the collateral compensation of the ipsilateral buccal nerve could innervate the sensation. And this process was regulated by TGF-β-Zfp423-ApoD pathway.
Dendritic cell vaccine trials in gliomas: Untangling the lines
Authors: Kelly M Hotchkiss, Kristen A Batich, Aditya Mohan, Rifaquat Rahman, Steven Piantadosi, Mustafa Khasraw
Journal: Neuro-Oncology (2023)

Abstract Glioblastoma is a deadly brain tumor without any significantly successful treatments to date. Tumor antigen-targeted immunotherapy platforms including peptide and dendritic cell (DC) vaccines, have extended survival in hematologic malignancies. The relatively “cold” tumor immune microenvironment and heterogenous nature of glioblastoma have proven to be major limitations to translational application and efficacy of DC vaccines. Furthermore, many DC vaccine trials in glioblastoma are difficult to interpret due to a lack of contemporaneous controls, absence of any control comparison, or inconsistent patient populations. Here we review glioblastoma immunobiology aspects that are relevant to DC vaccines, review the clinical experience with DC vaccines targeting glioblastoma, discuss challenges in clinical trial design, and summarize conclusions and directions for future research for the development of effective DC vaccines for patients.
Sonodynamic therapy combined with phototherapy: Novel synergistic strategy with superior efficacy for antitumor and antiinfection therapy
Authors: Haoyuan Hu, Jiahui Zhao, Kezhong Ma, Jiale Wang, Xinqi Wang, Tianlong Mao, Chunrong Xiang, Hao Luo, Ye Cheng, Mengran Yu, Youran Qin, Kaiqing Yang, Qian Li, Yao Sun, Songyun Wang
Journal: Journal of Controlled Release (2023)